Evidence That Schizophrenia is a Brain Disease

Rashmi Nemade, Ph.D. & Mark Dombeck, Ph.D.

Evidence That Schizophrenia is a Brain Disease

Data from modern scientific research proves that schizophrenia is unequivocally a biological disease of the brain, just like Alzheimer's Disease and Bipolar Disorder. For one thing, schizophrenia is now known to be partially caused by genetics and to be inherited. For another, modern non-invasive brain imaging techniques such as Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT), have documented structural differences between schizophrenic and normal brains. Individuals with schizophrenia have up to 25% less volume of gray matter in their brains, especially in the temporal and frontal lobes (known to be important for coordination of thinking and judgment). Patients demonstrating the worst brain tissue losses also tend to show the worst symptoms.

Functional scanning of the brain, using technologies like Positron Emission Tomography (PET) and functional MRI have made it possible to create real-time maps of regional cerebral blood flow and metabolism, providing another window into how schizophrenic brains are distinct from normal brains. Such studies tend to show low levels of activation in schizophrenic patients' middle frontal cortex and inferior parietal cortex compared to normal people included as control subjects. Low activity findings like this are also correlated with (related to) increased negative symptoms (meaning that people who tend to have more negative symptoms, also tend to show lower levels of brain activity in key brain areas).

Schizophrenic brains are thus (on average) different in terms of total tissue volume, and activity. However, there is most often no obvious single point of structural damage (a "lesion") to point at as the specific location in the brain where schizophrenia is happening.

In addition to structural differences, schizophrenic brains also show neurochemical differences when compared with normal brains. The brain uses a number of chemical messengers, called neurotransmitters, to communicate among its millions of individual neurons. At the most basic level, schizophrenic brains appear to be differentially sensitive to the neurotransmitter dopamine compared to normal brains. The "dopamine hypothesis" of schizophrenia holds that schizophrenia is caused by excess dopamine (or excessive sensitivity to dopamine). Support for this hypothesis comes from several main sources. First, drugs known to block the effects of dopamine in the brain are also known to be useful as antipsychotic medications (they reduce the intensity and frequency of hallucinations, for example). Second, stimulant drugs like cocaine and methamphamine, which are known to either mimic the action of dopamine, or to cause dopamine to become more active in the brain, are know to be capable of causing hallucinations and delusions in non-schizophrenic people (if enough of those substances are taken). It is also known that too little dopamine is responsible for Parkinson's disease, and that chronic use of antipsychotic medications (which block dopamine) can result in a Parkinson's-like condition called tardive dyskinesia.

While the dopamine hypothesis has been dominant for a long time, it has taken a research beating in recent years, and it is no longer so clear that dopamine alone is responsible for causing schizophrenia. Today, it appears more likely that other neurotransmitters are involved in creating conditions for schizophrenia and psychosis, including serotonin (implicated in depression and anxiety), and glutamate (which is known to be implicated in the hallucinatory effects of the drug PCP ("angel dust"). Though the details of neurochemical involvement in schizophrenia change as new findings accumulate, the essential neurochemical basis of schizophrenia has been quite firmly established and would now appear to be beyond question.

Considered as a group and compared to normal people, schizophrenics show observable functional deficits as well. Functional deficits are problems people have in performing basic mental and physical tasks and activities such as remembering things, using executive functioning (being able to flexibly shift between various tasks, making judgment, etc.), intuiting rules from consequences, and hand grip strength. On average, schizophrenic people show reduced memory, attention span, executive functioning, and reaction time compared to normal people. They have relatively more difficulty recalling things they learned five minutes before than normal people, for example, but are equally able to recall long-term memories. They tend to be more distractable and have a harder time engaging in problem solving and planning efforts than do normal people.

Abnormalities in sensory processing are also evident in schizophrenic patients. It is common for schizophrenic patients to show 'soft' neurological signs, meaning that they might have difficulty distinguishing between two simultaneous touches or in being able to identify numbers drawn on the palm of their hand. They also tend to confuse the right and left sides of their bodies more frequently than normal people. Such well documented observations of sensory processing problems suggest impairments or irregularities in the way that schizophrenics' brains are wired.

Still more evidence of neurological impairment in schizophrenia comes from consideration of electroencephalogram (EEG) data, which are tests of brain electrical activity. About one-third of schizophrenic people show abnormal electrical brain impulses, also suggesting irregularities in the way schizophrenic brains are wired.

Considered as a whole, these numerous and methodologically distinct results suggest converging and compelling evidence for the idea that schizophrenia is basically a biologically based brain disease.